Role of chloride concentration in modulating seizure transitions in excitatory and inhibitory networks

A research team led by Qianchen Gong, Yingpeng Liu, Yan Zhang, Muhua Zheng, and Kesheng Xu has published a significant computational neuroscience paper titled 'Role of chloride concentration in modulating seizure transitions in excitatory and inhibitory networks' in Physical Review E (2026). The study addresses a critical gap in understanding how activity-dependent chloride dynamics drive the evolution and stage transitions of seizures. While experimental evidence has shown that intracellular chloride concentration regulates the excitation-inhibition (EI) balance, the specific mechanisms remained unclear.

The researchers developed a sophisticated conductance-based neuronal network model in which EI balance emerges from chloride homeostasis through two primary mechanisms: channel-mediated chloride influx and transporter-mediated chloride extrusion. Their key finding is that the fraction of inhibitory synaptic conductance contributing to channel-mediated chloride influx acts as a crucial control parameter that organizes seizure dynamics into three distinct stages: pre-ictal, ictal-tonic, and ictal-clonic. Each stage exhibits characteristic amplitude and frequency signatures that can be identified and analyzed.

Their model reveals that decreasing this chloride influx fraction shortens ictal activity and suppresses seizure initiation, while high fractions promote the emergence of both ictal-tonic and ictal-clonic stages along with spiral-wave dynamics. At intermediate values, seizures bypass the ictal-tonic stage entirely and emerge directly as the ictal-clonic stage. Furthermore, the researchers discovered that joint variation of these fractions with synaptic strengths shows that recurrent excitation expands tonic-clonic seizures, while recurrent inhibition prolongs pre-ictal states and suppresses ictal-clonic activity.